2014-18 Water and electrolytes disturbances Sodium balance Fluid and Electrolyte Disturbances Water balance Hao, Chuan-Ming MD assium Composition of body Fluids Water is the most abundant constituent in the body 50% of body weight in women Total body water is distributed in two major intravascular(plasma water) and The major ECF particles: Na* CH and HCO3- The predominant ICF osmoles: K* and organic phosphate esters (ATP, creatine phosp and phospholipids 命HO Certain solutes, particularly urea, do ontribute to water shifts across most … membranes and are thus known as ineffective Cell shrinks
2014-1-8 1 Fluid and Electrolyte Disturbances Hao, Chuan-Ming MD Huashan Hospital Water and electrolytes disturbances • Sodium balance – Hypovolemia • Water balance – Hyponatremia – Hypernatremia • Potassium balance – Hypokelemia – hyperkelemia Composition of Body Fluids • Water is the most abundant constituent in the body: – 50% of body weight in women – 60% in men • Total body water is distributed in two major compartments: – 55–75% is intracellular fluid (ICF) – 25–45% is extracellular fluid (ECF) • ECF is subdivided into – intravascular (plasma water) and – extravascular (interstitial) spaces in a ratio of 1:3. 2/3 ECF 1/3 ECF Osmoles • The major ECF particles: Na+ , Cl– and HCO3 – • The predominant ICF osmoles: K+ and organic phosphate esters (ATP, creatine phosphate, and phospholipids) • Certain solutes, particularly urea, do not contribute to water shifts across most membranes and are thus known as ineffective osmoles
2014-18 Water and electrolytes disturbances Sodium balance In the steady state, urinary excretion of Hypovolemia sodium is closely matched to dietary salt Water balance Hyponatremia This balance depends Afferent mechanisms that sense the volume of the Potassium balance ECF compartment relative to its capacitance Hypovolemia A reduction in the volume of the ECF compartment in relation to its capacitance. bsolute hypovolemia, a deficit in sodium reflects The volume of the ecf intravascular and extravascular(interstitial) subcompartments may he same or opposite directions. ICF volume is reflected by plasma osm sodium concentration and may be co disturbed i:注 Causes of hypovolemia EXTRARENAL Clinical features ntestinal fluid loss(diarrhea, vomiting, ileostomy or colostomy secretions) History: vomiting, diarrhea, trauma. ird space loss ma states(heart failure, cirrhosis) Large and more acute fluid losses lead to hypovolemic shock Absolut vasoconstriction and hypoperfusion: (cyanosis, cold and clammy extremities, oliguria and Endocrine disorders(e.g, hypoaldosteronism, adrenal 2
2014-1-8 2 Water and electrolytes disturbances • Sodium balance – Hypovolemia • Water balance – Hyponatremia – Hypernatremia • Potassium balance – Hypokelemia – hyperkelemia Sodium Balance • In the steady state, urinary excretion of sodium is closely matched to dietary salt intake. • This balance depends on: • Afferent mechanisms that sense the volume of the ECF compartment relative to its capacitance • Effector mechanisms that modify the rate of renal sodium excretion Hypovolemia • A reduction in the volume of the ECF compartment in relation to its capacitance. • absolute hypovolemia, a deficit in sodium reflects negative sodium balance. • The volume of the ECF intravascular and extravascular (interstitial) subcompartments may vary in the same or opposite directions. • ICF volume is reflected by plasma osmolality and sodium concentration and may be concomitantly disturbed Causes of hypovolemia Clinical features • History: vomiting, diarrhea, trauma… • Symptoms: Thirst, postural dizziness, oliguria, cyanosis, • Signs of intravascular volume contraction: – decreased jugular venous pressure, – postural hypotension, – postural tachycardia • Large and more acute fluid losses lead to hypovolemic shock: hypotension, – tachycardia, – peripheral vasoconstriction and – hypoperfusion: (cyanosis, cold and clammy extremities, oliguria and altered mental status)
2014-18 Diagnosis 个BUN,个SC,个BUN/SCr(>20 UNa <20 mmol/L(exception: ATN, Vomiting) 音 Treatment Water and electrolytes disturbances Goal: restore normovolemia Sodium balance Mild volume contraction oral route Severe hypovolemia:Ⅳ Water balance Hypernatremia Hypokele Water Balan Disorders of tasis result Water balance is regulated mainly by hirst and urine concentrated iras helos Maximal urine osmolality: 1200 be excreted per day Active Na, Cl reabsorption in TAL
2014-1-8 3 Diagnosis • History & physical examination • Labs: – BUN, SCr, BUN/SCr (>20) – UNa <20 mmol/L (exception: ATN, Vomiting), – UCl < 20 mmol/L (GI) Treatment • Goal: restore normovolumia • Mild volume contraction: oral route • Severe hypovolemia: IV Water and electrolytes disturbances • Sodium balance – Hypovolemia • Water balance – Hyponatremia – Hypernatremia • Potassium balance – Hypokelemia – hyperkelemia Water Balance • Disorders of water homeostasis result in hypo- or hypernatremia • Water balance is regulated mainly by thirst and urine concentration mechanism • The principal determinant of renal water excretion is AVP • Maximal urine osmolality: 1200 mosmol/kg • Minimal urine osmolality: 50 mosmo/kg • Normally about 600 mosmols must be excreted per day • Filtration • Active Na, Cl reabsorption in TAL • AVP
2014-18 AVP Collecting duct principal cell or Blood Side AVP secretion mosmol/kg. AQP4 blood volume and blood pressure. Nonosmotic stimul: nausea, intracerebral angiotensin Il, serotonin, and multiple drugs Half-life in the circulation 10-20 min antidiuretic hormone(ADH) Response to Changes in Serum Osmolality AVP rine osmolality AVP secretion: systemic osmolality, threshold level of 285 S5mAximally effective osmol/kg. vasopressin levels blood volume and blood pressure. Nonosmotic stimul: nausea, intracerebral angiotensin Il, serotonin, and multiple drugs 80284288290294296 erum osmolality (mOsm/) Hypovolemia or hypotension Hyponatremia Plasma sodium concentration less than 135 Hypervolemia The most frequently encountered electrolyte 260270280290300310320330340
2014-1-8 4 AVP • AVP secretion: – systemic osmolality, threshold level of 285 mosmol/kg. – blood volume and blood pressure. • Nonosmotic stimul: nausea, intracerebral angiotensin II, serotonin, and multiple drugs. • Half-life in the circulation: 10–20 min AVP • AVP secretion: – systemic osmolality, threshold level of 285 mosmol/kg. – blood volume and blood pressure. • Nonosmotic stimul: nausea, intracerebral angiotensin II, serotonin, and multiple drugs. • Half-life in the circulation: 10–20 min Hyponatremia • Plasma sodium concentration less than 135 mmol/L, • The most frequently encountered electrolyte abnormality in hospitalized patients
2014-18 olar Disorde Depletion effective solutes such as Primary Decreases in Total Body solute very high concentrations of glucose in diabetic patients or Secondary Water Retention Isotonic hyponatremia: hyperlipidemia or marked perglobulinemia-pseudohyponatremia True hypotonic hyponatremia: portant underlying disorder that leads to abnormal dy water balanc the hypotonic state indicates either past or ongoing ution(Primary Increases in Total Body Water* Secondary Solute Primary Decreases in Total Body Solute Secondary Water Impaired Renal Free Water Excretion Retention mpaired Distal Dilution inappropriate antidiuretic hormone secretion(SIADH) Combined Increased Proximal Reabsorption and impa ired Distal Nonrenal Solute Loss Gastrointestinal (diarrhea, vomiting, pancreatitis, bowel Congestive heart failure obstruction utaneous(sweating, burns Blood loss Decreased Urinary Solute Excretion Beer pototan Excess Water Intake Diagnostic Criteria for the Syndrome of Inappropriate ADH Release AL NERVOUS SYSTEM DISORDER Essential Diagnostic Criteria 1 c2ro mosman H or mud erective osmoasly Inappropriate urinary concentration (>100 mosm/kg H2 O) PULMONARY DESORDEI DH Elevated urinary Na concentration under conditions of normal Absence of adrenal, thyroid, pituitary, or renal insufficiency or ED Criterin 物bm H level inappropriately elevated relative to No significant correction af plasma Na level with volume 5
2014-1-8 5 • Hypertonic hyponatremia: an accumulation in the ECF compartment of non-sodium-containing effective solutes such as – very high concentrations of glucose in diabetic patients or – exogenously administered mannitol or glycerol. • Isotonic hyponatremia: hyperlipidemia or marked hyperglobulinemia – pseudohyponatremia • True hypotonic hyponatremia: – an important underlying disorder that leads to abnormal body water balance, – the hypotonic state indicates either past or ongoing expansion of ICF volume. Hypo-osmolar Disorders • Depletion: – Primary Decreases in Total Body Solute + Secondary Water Retention • Dilution: – Primary Increases in Total Body Water ± Secondary Solute Depletion Causes of SIADH
2014-18 Clinical features Clinical manifestations are related to osmotic ading to increased ICF, specifically brain swell or cerebral ly neurologic and rapidity of onset and Symptoms include headache, lethargy, seizures, and a ogress to coma and death. The severity of these neurologic manifestations depends more on the rate of the hypotonic decline in plasma sodium If a patient survives the acute hyponatremia, osmotic adaptation tends to mitigate the symptoms of cerebral edema t↓ Treatment Treatment of hyponatremia varies depending on the It is the importance of identifying and treating any underlying disorder urologic status, and any information about recent
2014-1-8 6 Clinical features • Clinical manifestations are related to osmotic water shift leading to increased ICF, specifically brain swell or cerebral edema. Therefore, the symptoms are primarily neurologic and their severity is dependent on the rapidity of onset and absolute decrease in plasma [Na+]. • Symptoms include headache, lethargy, seizures, and a progressively decreased level of consciousness that can progress to coma and death. • The severity of these neurologic manifestations depends more on the rate of the hypotonic decline in plasma sodium concentration. • If a patient survives the acute hyponatremia, osmotic adaptation tends to mitigate the symptoms of cerebral edema. Treatment • Treatment of hyponatremia varies depending on the category and underlying diagnosis • It is the importance of identifying and treating any underlying disorder • The sodium concentration and the rate of correction should be guided by the patient’s age, gender, neurologic status, and any information about recent past plasma sodium concentrations or osmolality values
2014-18 Delayed correction of hyponatremia can perpetuate ebral edema and result in irreversible neurologic damage and death In contrast, too rapid correction can result in the nd recovery in nonfatal cases is either slow incomplete, often with irreversible residual Acute Hypotonic Hyponatremia Chronic Hyponatremia (<24 to 48 hours) symptoms such as seizure consciousness, correction odium concentration should not exceed 8 reach a target sodium concentration. e first 24 hours in euvolemic patients The desired rise in sodium concentration should not exceed 2 mmol /L/hour, and the total increase in sodium concentration during the first 12 to 24 hours of treatment should not exceed 12 mmol/L Normovolemic hyponatre Hypovolemic Hypotonic Hyponatrer In patients with normovolemic hyponatremia the appropriate therapeutic approach is to address the underlying disease Water restriction lium concentration in the setting of extrarenal fluid Great caution should be exercised in the administration of a brisk and rapid decrease in urine osmolality 7
2014-1-8 7 • Delayed correction of hyponatremia can perpetuate cerebral edema and result in irreversible neurologic damage and death. • In contrast, too rapid correction can result in the osmotic demyelination syndrome, which can be fatal, and recovery in nonfatal cases is either slow or incomplete, often with irreversible residual neurologic sequelae Acute Hypotonic Hyponatremia (<24 to 48 hours) • If patient is accompanied by severe neurologic symptoms such as seizures or decreased level of consciousness, correction should be rapid and should reach a target sodium concentration. • The desired rise in sodium concentration should not exceed 2 mmol/L/hour, and the total increase in sodium concentration during the first 12 to 24 hours of treatment should not exceed 12 mmol/L. Chronic Hyponatremia • In such cases, the targeted rate of increase in sodium concentration should not exceed 0.5 mmol/L/hour, and the total rise in sodium concentration should not exceed 8 mmol/L in the first 24 hours • Water restriction is helpful in euvolemic patients Normovolemic hyponatremia • In patients with normovolemic hyponatremia, the appropriate therapeutic approach is to address the underlying disease • Water restriction • V2 receptor antagonist Hypovolemic Hypotonic Hyponatremia • When hypovolemia is clearly evident, administration of volume repletion in the form of isotonic saline is the treatment of choice – appropriate clinical history, – orthostatic hypotension, – low urine sodium concentration in the setting of extrarenal fluid losses, – elevated plasma urea and uric acid concentrations • Great caution should be exercised in the administration of isotonic saline to these patients because sometimes the administration of small volumes of isotonic saline can induce a brisk and rapid decrease in urine osmolality
2014-18 Treatment Hypernatremia Treat the underlying disease, if possible Hypernatremia, defined as a plasma sodium concentration greater than 144 mmol/L, ral or intravenous sodium chloride in patients with true always reflects a state of hypertonicity. Sodium chloride administration is also effective in patients the (SIADH)using either oral salt tablets or hypertonic saline. rast, isotonic saline is often not effective and may orsen the hyponatremia in SIADH Administration of a vasopressin receptor antagonist Causes of hypernatremia Diabetes insipidus(Dl) Hypovolemia: associated with low total body sodium of both Na+ and water, but with a relatively greater los Patients with central and nephrogenic DI and primary Hypervolemia: associated with increased total body sodium mia: hypertonic saline solutions have emerged eferable alternative to mannitol for treatment of inert complished by clinical evaluation, with measurements of vasopressin level and Euvolemia: associated with normal body sodium response to a water deprivation test followed by vasopressin Most patients with hypernatremia secondary to water loss appear dy Na+ because loss of water without Na+ does not lead to Clinical Manifestations Central Diabetes Insipidus Congenital Nephrogenic Diabetes Insipidus red mental status, lethargy irritability restlessness, seizures(usually in children), muscle twitching, hyperreflexia Fever, nausea or vomiting, labored breathing, and intense mol/l are associated with a 75% mortality, although this may reflect associated comorbidities rather than hypernatremia per se 8
2014-1-8 8 Treatment • Treat the underlying disease, if possible. • Fluid restriction. • Oral or intravenous sodium chloride in patients with true volume depletion. • Sodium chloride administration is also effective in patients the syndrome of inappropriate antidiuretic hormone secretion (SIADH) using either oral salt tablets or hypertonic saline. • In contrast, isotonic saline is often not effective and may worsen the hyponatremia in SIADH • Administration of a vasopressin receptor antagonist Hypernatremia • Hypernatremia, defined as a plasma sodium concentration greater than 144 mmol/L, always reflects a state of hypertonicity. Causes of Hypernatremia • Hypovolemia: associated with low total body sodium – losses of both Na+ and water, but with a relatively greater loss of water • Hypervolemia: associated with increased total body sodium – administration of hypertonic solutions such as 3% NaCl, NaHCO3. – Therapeutic hypernatremia: hypertonic saline solutions have emerged as a preferable alternative to mannitol for treatment of increased intracranial pressure. • Euvolemia: associated with normal body sodium – Most patients with hypernatremia secondary to water loss appear euvolemic with normal total body Na+ because loss of water without Na+ does not lead to overt volume contraction Diabetes insipidus (DI) • Characterized by polyuria and polydipsia • Caused by defects in vasopressin action. • Patients with central and nephrogenic DI and primary polydipsia present with polyuria and polydipsia. • The differentiation between these entities can be accomplished by clinical evaluation, with measurements of – vasopressin levels and – the response to a water deprivation test followed by vasopressin administration • Central Diabetes Insipidus • Congenital Nephrogenic Diabetes Insipidus • Acquired Nephrogenic Diabetes Insipidus Clinical Manifestations • Signs and symptoms mostly relate to the CNS and include altered mental status, lethargy, irritability, restlessness, seizures (usually in children), muscle twitching, hyperreflexia, and spasticity. • Fever, nausea or vomiting, labored breathing, and intense thirst can also occur. • In adults, serum Na+ concentrations above 160 mmol/l are associated with a 75% mortality, although this may reflect associated comorbidities rather than hypernatremia per se
2014-18 Treatment of Hypernatremia Hypernatremia occurs in predictable clinical settings, llowing opportunities for prevention Route: mouth or via a nasogastric tube or 5% uncontrolled diabetes Low salt diet low-dose thiazide diuretics Drugs that stimulate AVP section or enhance its action Water deficit should be corrected slowly over 48 72h. The plasma Na concentration be lowered by 0.5 mmol/,/h and by no more than 12 mmol/ L over the Water and electrolytes disturbances Sodium balance Water balance Potassium balance Potassium balance K intake: 1 mmol/kg/d Distribution of Total Body Potassium in Organs Immediately following a meal, most K enter and Body Compartments excretion 4 mmoll
2014-1-8 9 Treatment of Hypernatremia • Hypernatremia occurs in predictable clinical settings, allowing opportunities for prevention – recovery from acute kidney injury, – catabolic states, – therapy with hypertonic solutions, – uncontrolled diabetes – burns • Water deficit should be corrected slowly over 48 – 72h. The plasma Na concentration be lowered by 0.5 mmol/l/h and by no more than 12 mmol/L over the 1 st 24h • Route: mouth or via a nasogastric tube or 5% dextrose or half-isotonic saline iv • CDI – Desmopressin – Low salt diet + low-dose thiazide diuretics – Drugs that stimulate AVP section or enhance its action Water and electrolytes disturbances • Sodium balance – Hypovolemia • Water balance – Hyponatremia – Hypernatremia • Potassium balance – Hypokelemia – hyperkelemia Potassium balance • K intake: 1 mmol/kg/d • Immediately following a meal, most K enter cells (plasma K, insulin, catecholamine) • Steady state, K ingestion matches with excretion
2014-18 Potassium excretion he filtered K is 10-2 K delivery to distal tubule Im delivery and high levels of aldo total body k balance occurs in K secretion is increased distal Na delivery Hypokalel Hypokalemia versus Potassium Deficiency Etiology Potassium deficiency is the state that results from a persistent negative potassium balance Increased net loss Hypokalemia refers to a low plasma [K+]. extrarenal potassium loss inadequate potassium intake or excessive potassium tassium loss losses)or from a net shift of K+ from the ecf to the
2014-1-8 10 Potassium excretion • The filtered K is 10 -20 fold of ECF K content • 90% of filtered K is reabsorbed in proximal tubule and loop of Henle • K delivery to distal tubule proximate dietary intake • All regulation of renal K excretion an total body K balance occurs in the distal nephron • K secretion is regulated by aldosterone and hyperkalemia • K secretion is facilitated by increased distal Na delivery High sodium delivery and high levels of aldo Hypokalemia Hypokalemia versus Potassium Deficiency • Potassium deficiency is the state that results from a persistent negative potassium balance • Hypokalemia refers to a low plasma [K+]. • Hypokalemia can result from potassium deficiency (inadequate potassium intake or excessive potassium losses) or from a net shift of K+ from the ECF to the ICF compartment. • A patient may have severe potassium depletion without manifesting hypokalemia (diabetes ketoacidosis) Etiology • Redistribution • Increased net loss: – extrarenal potassium loss – renal potassium loss • Decreased net intake • Pseudohypokalemia
